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Vaccines - Human Vaccines

There are three vaccines that are commercially available at this time: the Georgian/Russian, the UK, and the US vaccines. All three are derived from an avirulent strain of Bacillus anthracis called the Sterne strain. This strain lacks the plasmid pX02 which encodes the protecive coating of the bacteria. The Georgian/Russian vaccine, produced by the Tblisi Research institute of Vaccines and Serums, consists of live spores from the Sterne strain administered in the shoulder by scarification. Its efficacy is unknown but it is reputed to have a high number of side effects and contraindications (17).

The UK and US vaccines consist of alum-precipitated cell-free filtrates of bacilli. In other words, these vaccines consist of solutions containing the protective antigen PA. The US vaccine is alternately called AVA for anthrax vaccine absorbed and MDPH since it was initially manufactured by the Michigan Department of Health. The difference between the US and UK vaccines is that AVA is absorbed onto aluminum hydroxide, a member of the only family adjuvants that is approved for use in humans. Aluminum Hydroxide boosts the humoral response (14). Both vaccines are produced in a manner to maximize the content of PA and minimize the content of EF and LF (17).

Vaccination consists of six initial doses at 0, 2, and 4 weeks and 6, 12, and 18 months followed by a yearly booster. In the UK the first three doses are three weeks apart. As expected, both vaccines manage to increase the bodies response to PA in the form of increased IgG. However, despite the name of protective antigen, high antibody levels do not correlate with an immune state. In fact the actual correlate of immunity for anthrax is not known at this time. Antibodies are important but haven't been the deciding factor in animal models.

There are a couple of problems with the current US and UK vaccines. The immunization schedule demonstrates that the vaccine is poor in generating immunological memory. Numerous studies testing the efficacy of the vaccines in animals have met with mixed results. For example, Guinea Pigs immunized with AVA have done well when challenged with certain strains of Anthrax but not so well when challenged with other strains (12). Furthermore, due to the nature of cell-free filtrate procedures, the vaccine contains a mixture of undefined bacterial products, and thus the potency of has been found to vary from lot to lot (14).

Fortunately, because of the low occurence in humans it seems that we may be naturally resistant to some degree. The down side of this is that the low incidence rate has made it extremely hard to characterize the disease when it does strike. To date there have been only two large scale trials that have managed to assess to some degree the efficacy of our current vaccines:

The protection reported in the Brachman study was to cutaneous anthrax only. The study lacked the statistical size needed to assess the protection to inhalation anthrax. The Burgasov study did not differentiate between the two forms of the disease (17). Since this study the US vaccine has been altered to include four to six fold higher concentrations of PA (12).

The study often cited in support of the US vaccine was performed by Ivins et al. In the study rhesus macaques were immunized with two doses of vaccine prior to exposure with a lethal dose of aerosolized anthrax spores. The unvaccinated monkeys all died within five days of exposure, whereas the vaccinated monkeys were protected up to two years (19). The idea is that since macaques are closer to humans phylogenetically, the results of this study should carry more weight than the studies involving guinea pigs and mice. However, Ivins et al only tested with one strain of Bacillus Anthracis and other species are known to have different susceptibilities to different strains (16).

In addition to questions of efficacy, there are also questions of ethics. In the US the principle buyer and administrator of AVA is the US military.